Investigation of the curative effect of losartan on the diabetes mellitus by GC-based metabonomics

The aim of the study was to assess the feasibility of metabonomics in clinical studies and the curative effect of drug. It is projected that type 2 diabetes will be the biggest killer in the western world by 2020. Diabetic Nephropathy (DN) is the main chronicity complication of Diabetes Mellitus (DM). Losartan, a kind of hypertension-drug, was found to have some curative effect to diabetes mellitus. The current GC pattern recognition (PR) approach to investigating the dose-related and the time-related metabolic effects of drug is described by the metabonomics platform. Diabetes Mellitus patients were dosed with Losartan (dose a and b) and urine was collected at 8 weeks and 12 weeks. Firstly the biochemical criterions (blood pressure, urinary albumen, urinary 8－OHdG and blood creatinine) were analyzed. Then urine samples were derivatived and analyzed by GC. After alignment the data were treated with multivariate analysis. The result indicated metabonomics analysis had special advantages and could show metabolic differences and biochemical variation associated with the drug, although the single biochemical criterion could not. When the method was applied to the clinical pharmacology, we could see dose a was the suited dose and the drug had better effect on patients after 12 weeks than after 8 weeks. Thus, the GC-based metabonomics analysis has enabled the rapid identification of significant metabolic differences and provided information concerning evaluation of the curative effect of Losartan. This is the first in vivo study demonstrating the endogenous metabolic effects of Losartan to Diabetic Nephropathy for the analysis of urine in a metabonomics study which shown potential advantages compared with biochemical criterion